Actin-binding protein profilin1 is an important determinant of cellular phosphoinositide control.

Membrane polyphosphoinositides (PPIs) are lipid-signaling molecules that undergo metabolic turnover and influence a diverse range of cellular functions. PPIs regulate the activity and/or spatial localization of a number of actin-binding proteins (ABPs) through direct interactions; however, it is much less clear whether ABPs could also be an integral part in regulating PPI signaling. In this study, we show that ABP profilin1 (Pfn1) is an important molecular determinant of the cellular content of PI(4,5)P2 (the most abundant PPI in cells). In growth factor (EGF) stimulation setting, Pfn1 depletion does not impact PI(4,5)P2 hydrolysis but enhances plasma membrane (PM) enrichment of PPIs that are produced downstream of activated PI3-kinase, including PI(3,4,5)P3 and PI(3,4)P2, the latter consistent with increased PM recruitment of SH2-containing inositol 5' phosphatase (SHIP2) (a key enzyme for PI(3,4)P2 biosynthesis). Although Pfn1 binds to PPIs in vitro, our data suggest that Pfn1's affinity to PPIs and PM presence in actual cells, if at all, is negligible, suggesting that Pfn1 is unlikely to directly compete with SHIP2 for binding to PM PPIs. Additionally, we provide evidence for Pfn1's interaction with SHIP2 in cells and modulation of this interaction upon EGF stimulation, raising an alternative possibility of Pfn1 binding as a potential restrictive mechanism for PM recruitment of SHIP2. In conclusion, our findings challenge the dogma of Pfn1's binding to PM by PPI interaction, uncover a previously unrecognized role of Pfn1 in PI(4,5)P2 homeostasis and provide a new mechanistic avenue of how an ABP could potentially impact PI3K signaling byproducts in cells through lipid phosphatase control.

Vascular endothelial profilin-1 drives a protumorigenic tumor microenvironment and tumor progression in renal cancer.

Overexpression of actin-binding protein profilin-1 (Pfn1) correlates with advanced disease features and adverse clinical outcome of patients with clear cell renal carcinoma, the most prevalent form of renal cancer. We previously reported that Pfn1 is predominantly overexpressed in tumor-associated vascular endothelial cells in human clear cell renal carcinoma. In this study, we combined in vivo strategies involving endothelial cell-specific depletion and overexpression of Pfn1 to demonstrate a role of vascular endothelial Pfn1 in promoting tumorigenicity and enabling progressive growth and metastasis of renal carcinoma cells in a syngeneic orthotopic mouse model of kidney cancer. We established an important role of endothelial Pfn1 in tumor angiogenesis and further identified endothelial Pfn1-dependent regulation of several pro- (VEGF, SERPINE1, CCL2) and anti-angiogenic factors (platelet factor 4) in vivo. Endothelial Pfn1 overexpression increases tumor infiltration by macrophages and concomitantly diminishes tumor infiltration by T cells including CD8+ T cells in vivo, correlating with the pattern of endothelial Pfn1-dependent changes in tumor abundance of several prominent immunomodulatory cytokines. These data were also corroborated by multiplexed quantitative immunohistochemistry and immune deconvolution analyses of RNA-seq data of clinical samples. Guided by Upstream Regulator Analysis of tumor transcriptome data, we further established endothelial Pfn1-induced Hif1α elevation and suppression of STAT1 activation. In conclusion, this study demonstrates for the first time a direct causal relationship between vascular endothelial Pfn1 dysregulation, immunosuppressive tumor microenvironment, and disease progression with mechanistic insights in kidney cancer. Our study also provides a conceptual basis for targeting Pfn1 for therapeutic benefit in kidney cancer.

Deciphering the drug delivery potential of Type1 lipid transfer protein from Citrus sinensis for enhancing the therapeutic efficacy of drugs.

Type1 Non-specific Lipid Transfer Protein (CsLTP1) from Citrus sinensis is a small cationic protein possessing a long tunnel-like hydrophobic cavity. CsLTP1 performing membrane trafficking of lipids is a promising candidate for developing a potent drug delivery system. The present work includes in-silico studies and the evaluation of drugs binding to CsLTP1 using biophysical techniques along with the investigation of CsLTP1's ability to enhance the efficacy of drugs employing cell-based bioassays. The in-silico investigations identified Panobinostat, Vorinostat, Cetylpyridinium Chloride, and Fulvestrant with higher affinities and stability of binding to the hydrophobic pocket of CsLTP1. SPR studies revealed strong binding affinities of anticancer drugs, Panobinostat (KD = 1.40 µM) and Vorinostat (KD = 2.17 µM) to CsLTP1 along with the binding and release kinetics. CD and fluorescent spectroscopy revealed drug-induced conformational changes in CsLTP1. CsLTP1-associated drug forms showed remarkably enhanced efficacy in MCF-7 cells, representing increased cell cytotoxicity, intracellular ROS, reduced mitochondrial membrane potential, and up-regulation of proapoptotic markers than the free drugs employing qRT-PCR and western blot analysis. The findings demonstrate that CsLTP1 binds strongly to hydrophobic drugs to facilitate their transport, hence improving their therapeutic efficacy revealed by the in-vitro investigations. This study establishes an excellent foundation for developing CsLTP1-based efficient drug delivery system.

Health-related quality of life and its determinants among cancer patients: evidence from 12,148 patients of Indian database.

BACKGROUND: Cancer survivors experience a decrement in health-related quality of life (HRQoL) resulting from the disease as well as adverse effects of therapy. We evaluated the HRQoL of cancer patients, stratified by primary cancer site, stage, treatment response and associated adverse events, along with its determinants. METHODS: Data were collected from 12,148 patients, sampled from seven purposively chosen leading cancer hospitals in India, to elicit HRQoL using the EuroQol questionnaire comprising of 5-dimensions and 5-levels (EQ-5D-5L). Multiple linear regression was used to determine the association between HRQoL and various socio-demographic as well as clinical characteristics. RESULTS: Majority outpatients (78.4%) and inpatients (81.2%) had solid cancers. The disease was found to be more prevalent among outpatients (37.5%) and inpatients (40.5%) aged 45-60 years and females (49.3-58.3%). Most patients were found to be in stage III (40-40.6%) or stage IV (29.4-37.3%) at the time of recruitment. The mean EQ-5D-5 L utility score was significantly higher among outpatients [0.630 (95% CI: 0.623, 0.637)] as compared to inpatients [0.553 (95% CI: 0.539, 0.567)]. The HRQoL decreased with advancing cancer stage among both inpatients and outpatients, respectively [stage IV: (0.516 & 0.557); stage III (0.609 & 0.689); stage II (0.677 & 0.713); stage I (0.638 & 0.748), p value < 0.001]. The outpatients on hormone therapy (B = 0.076) showed significantly better HRQoL in comparison to patients on chemotherapy. However, palliative care (B=-0.137) and surgery (B=-0.110) were found to be associated with significantly with poorer HRQoL paralleled to chemotherapy. The utility scores among outpatients ranged from 0.305 (bone cancer) to 0.782 (Leukemia). Among hospitalized cases, the utility score was lowest for multiple myeloma (0.255) and highest for testicular cancer (0.771). CONCLUSION: Older age, lower educational status, chemotherapy, palliative care and surgery, advanced cancer stage and progressive disease were associated with poor HRQoL. Our study findings will be useful in optimising patient care, formulating individualized treatment plan, improving compliance and follow-up.

Patterns of failure in patients with nasopharyngeal cancer of Northeastern region of India: a retrospective observational study.

PURPOSE: We aimed to analyze patterns of failure and disease volume-treatment outcomes in patients with Nasopharyngeal carcinoma (NPC) treated with definitive radiation with or without concurrent chemotherapy at a tertiary cancer centre in northeast India. METHODS: From February 2018 to February 2022, 99 histopathologically proved non-metastatic NPC patients treated with curative-intent RT with or without chemotherapy were retrospectively analyzed. Locally advanced patients received neoadjuvant or adjuvant chemotherapy. The Cox proportional hazards model was used to investigate the impact of various prognostic factors on locoregional free survival (LRFS), distant metastasis free survival (DMFS), progression free survival (PFS) and overall survival (OS). The log-rank test and Kaplan-Meir curves compared outcome variables based on ROC analysis-classified tumor volume. RESULTS: During a median follow up of 25.4 months (17.3-39.2), 35(35.4%) patients developed recurrence. Twenty-three patients developed locoregional failures, of which 11 were in-field; 12 patient showed an out-field failure. The 3-year LRFS, DMFS, PFS and OS was 71.10%, 70.90%, 64.10% and 74.10% respectively. There was statistically significant difference in LRFS according to T staging (p < 0.0001). Gross tumor volume (GTVp) and gross nodal volume (GTVn) were an independent prognostic factor for OS, PFS, LRFS and DMFS. The cut-off volumes for GTVp and GTVn for distant metastases and locoregional failure, respectively, were found to be 13 and 22.7 mL and 3.7 and 39.2 mL, respectively, by ROC curve analysis. Based on this, 99 patients were divided into three subgroups. OS demonstrated significant differences among patients in different volume subgroups for GTVp (p = 0.03) and GTVn (p = 0.00024). CONCLUSIONS: For NPC patients who undergo curative IMRT, primary tumour and nodal volumes are independent prognostic indicators. GTVp and GTVn are highly predictive of local control, distant metastases, disease-free survival, and overall survival. This justifies their use as quantitative prognostic indicator for NPC.

Green synthesized cobalt nanoparticles from Trianthema portulacastrum L. as a novel antimicrobials and antioxidants.

Trianthema portulacastrum is a dietary and medicinal plant that has gained substantial importance due to its pharmacological properties. This plant was used for its various healing properties since the ancient period in ayurvedic system of medicine. The green synthesis technique is an eco-friendly as well as cost effective technique which can produce more biocompatible nanoparticles when compared with those fabricated by physio-chemical methods. Therefore, nanoparticles produced by green synthesis are credible alternatives to those which are produced by conventional synthesis techniques. This research mainly aims to produce nanoparticles with the methanolic leaf extract of T. portulacastrum. The optimized nanoparticles were further analyzed for anti-fungal, anti-bacterial and antioxidant properties. Disk diffusion assay was used for the determination of the antimicrobial property and on the other hand, DPPH radical scavenging assay as well as hydrogen peroxide scavenging activity proved the antioxidant property of the formulation. The study revealed that Escherichia coli (gram negative strain) shows greater zone of inhibition when compared with Bacillus subtilis (gram positive bacteria). The nanoparticles have also been reported to show significant anti-fungal activity against the strains of Aspergillus niger and Fusarium oxysporum which proves its desirability for its further use against both bacterial as well as fungal infections. The novel formulation can be explored dually as antimicrobial and antioxidant agent.

Sulisobenzone is a potent inhibitor of the global transcription factor Cra.

Transcription is carried out by the RNA polymerase and is regulated through a series of interactions with transcription factors. Catabolite activator repressor (Cra), a LacI family transcription factor regulates the virulence gene expression in Enterohaemorrhagic Escherichia coli (EHEC) and thus is a promising drug target for the discovery of antivirulence molecules. Here, we report the crystal structure of the effector molecule binding domain of Cra from E. coli (EcCra) in complex with HEPES molecule. Based on the EcCra-HEPES complex structure, ligand screening was performed that identified sulisobenzone as an potential inhibitor of EcCra. The electrophoretic mobility shift assay (EMSA) and in vitro transcription assay validated the sulisobenzone binding to EcCra. Moreover, the isothermal titration calorimetry (ITC) experiments demonstrated a 40-fold higher binding affinity of sulisobenzone (KD 360 nM) compared to the HEPES molecule. Finally, the sulisobenzone bound EcCra complex crystal structure was determined to elucidate the binding mechanism of sulisobenzone to the effector binding pocket of EcCra. Together, this study suggests that sulisobenzone may be a promising candidate that can be studied and developed as an effective antivirulence agent against EHEC.

The role of profilin-1 in cardiovascular diseases.

Dynamic remodeling of the actin cytoskeleton is an essential feature for virtually all actin-dependent cellular processes, including cell migration, cell cycle progression, chromatin remodeling and gene expression, and even the DNA damage response. An altered actin cytoskeleton is a structural hallmark associated with numerous pathologies ranging from cardiovascular diseases to immune disorders, neurological diseases and cancer. The actin cytoskeleton in cells is regulated through the orchestrated actions of a myriad of actin-binding proteins. In this Review, we provide a brief overview of the structure and functions of the actin-monomer-binding protein profilin-1 (Pfn1) and then discuss how dysregulated expression of Pfn1 contributes to diseases associated with the cardiovascular system.

Titania Nanorod-Supported Mercaptoundecanoic Acid-Grafted Palladium Nanoparticles as a Highly Reusable Heterogeneous Catalyst for Substrate-Dependent Ullmann Coupling and Debromination of Aryl Bromides.

Herein, by implanting palladium nanoparticles (Pd NPs) onto titanium dioxide (TiO2) nanorods (NRs) through 11-mercaptoundecanoic acid (MUA), we devised a robust heterogeneous catalyst. The formation of Pd-MUA-TiO2 nanocomposites (NCs) was authenticated using Fourier transform infrared spectroscopy, powder X-ray diffraction, transmission electron microscopy, energy-dispersive X-ray analysis, Brunauer-Emmett-Teller analysis, atomic absorption spectroscopy, and X-ray photoelectron spectroscopy techniques. Pd NPs were synthesized directly onto TiO2 nanorods without the MUA support for comparative studies. As a means of evaluating the endurance and competency of Pd-MUA-TiO2 NCs compared to their counterpart (Pd-TiO2 NCs), both were used as the heterogeneous catalyst for Ullmann coupling of a wide variety of aryl bromides. When Pd-MUA-TiO2 NCs were used, the reaction produced high yields of homocoupled products (54-88%), whereas the yield was only 76% when Pd-TiO2 NCs were used. Moreover, Pd-MUA-TiO2 NCs impressed with their outstanding reusability property, allowing over 14 reaction cycles without losing efficiency. On the flip side, just after seven reaction cycles, the productivity of Pd-TiO2 NCs dropped around 50%. Presumably, the strong affinity of Pd for the thiol groups of MUA allowed for the substantial control of leaching out of Pd NPs during the reaction. Nonetheless, another crucial feature of the catalyst is that the di-debromination reaction took place with an excellent yield of 68-84% from di-aryl bromides with long alkyl chains instead of macrocyclic or dimerized products. It is worth mentioning that AAS data confirmed that only 0.30 mol % catalyst loading was sufficient to activate a broad substrate scope with large functional group tolerance.

Consumption of honey ameliorates lipopolysaccharide-induced intestinal barrier dysfunction via upregulation of tight junction proteins.

PURPOSE: The leaky gut barrier is an important factor leading to various inflammatory gastrointestinal disorders. The nutritional value of honey and variety of its health benefits have long been recognized. This study was undertaken to assess the role of Indian mustard honey in preventing lipopolysaccharide (LPS)-induced intestinal barrier dysfunction using a combination of in vitro and in vivo experimental model systems. METHODS: LPS was used to induce intestinal barrier damage in a trans-well model of Caco-2 cells (1 µg/ml) and in Swiss albino mice (5 mg/kg body weight). Gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) were used to analyse sugar and phenolic components in honey samples. The Caco-2 cell monolayer integrity was evaluated by transepithelial electrical resistance (TEER) and paracellular permeability assays. The histopathology of intestinal tissue was analysed by haematoxylin and eosin dual staining. The quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to quantify the transcription of genes. The protein expression was analysed by immunofluorescence, western blot and ELISA-based techniques. RESULTS: The in vitro data showed that honey prevented LPS-induced intestinal barrier dysfunction dose dependently as was measured by TEER and paracellular flux of FITC-dextran dye. Further, the in vivo data showed a prophylactic effect of orally administered honey as it prevented the loss of intestinal barrier integrity and villus structure. The cellular localization and expression of tight junction (TJ) proteins were upregulated along with downregulation of pro-inflammatory cytokines in response to the administration of honey with LPS. CONCLUSIONS: The findings of this study suggest a propitious role of honey in the maintenance of TJ protein integrity, thereby preventing LPS-induced intestinal barrier disintegration.

Synthesis of amide derivatives of 3-aryl-3H-benzopyrans as osteogenic agent concomitant with anticancer activity.

The present study reports a series of 3-aryl-3H-benzopyran-based amide derivatives as osteogenic agents concomitant with anticancer activity. Six target compounds viz 22e, 22f, 23i, and 24b-d showed good osteogenic activity at 1 pM and 100 pM concentrations. One of the potential molecules, 24b, effectively induced ALP activity and mRNA expression of osteogenic marker genes at 1 pM and bone mineralization at 100 pM concentrations. These molecules also presented significant growth inhibition of osteosarcoma (MG63) and estrogen-dependent and -independent (MCF-7 and MDA-MB-231) breast cancer cells. The most active compound, 24b, inhibited the growth of all the cancer cells within the IC50 10.45-12.66 µM. The mechanistic studies about 24b showed that 24b induced apoptosis via activation of the Caspase-3 enzyme and inhibited cancer cell migration. In silico molecular docking performed for 24b revealed its interaction with estrogen receptor-ß (ER-ß) preferentially.

A Smartphone-Enabled Imaging Device for Chromotropic Acid-Based Measurement of Nitrate in Soil Samples.

In this study, a novel chromotropic acid-based color development method was proposed for quick estimation of soil nitrate (NO3-). The method utilized a 3D printed device integrated with the rear-end camera of a smartphone and a stand-alone application called SMART NP. By analyzing the mean Value (V) component of the sample's image, the SMART NP provides instant predictions of soil NO3- levels. The limit of detection was calculated as 0.1 mg L-1 with a sensitivity of 0.26 mg L-1. The device showed a % bias of 0.9% and a precision of 1.95%, indicating its reliability. Additionally, the device-predicted soil NO3- data, combined with kriging interpolation, showcased spatial variability in soil NO3- levels at the regional level. The study employed a Gaussian model of variogram for kriging, and the high Nugget/Sill ratio indicated low spatial autocorrelation, emphasizing the impact of management factors on the spatial distribution of soil NO3- content in the study area. Overall, the imaging device, along with geostatistical interpolation, provided a comprehensive solution for the rapid assessment of spatial variability in soil NO3-content.

Detection of endocrine and metabolism disrupting xenobiotics in milk-derived fat samples by fluorescent protein-tagged nuclear receptors and live cell imaging.

Nuclear receptors (NRs) are ligand-modulated transcription factors that regulate multiple physiological functions in our body. Many NRs in their unliganded state are localized in the cytoplasm. The ligand-inducible nuclear translocation of NRs provides a valuable tool for studying the NR-ligand interactions and their downstream effects. The translocation response of NRs can be studied irrespective of the nature of the interacting ligand (agonist, antagonist, or a small molecule modulator). These nuclear translocation studies offer an advantage over promoter-reporter-based transcription assays where transcription response is observed only with the activating hormones or agonistic ligands. Globally, milk serves as a major dietary source. However, suspected presence of endocrine/metabolism-disrupting chemicals like bisphenols, parabens, organochlorine pesticides, carbamates, non-steroidal anti-inflammatory drugs, chloramphenicol, brominated flame retardants, etc. has been reported. Considering that these chemicals may impart serious developmental and metabolism-related health concerns, it is essential to develop assays suitable for the detection of xenobiotics present at differing levels in milk. Since milk samples cannot be used directly on cultured cells or for microscopy, a combination of screening strategies has been developed herein based on the revelation that i) lipophilic NR ligands can be successfully retrieved in milk-fat; ii) milk-fat treatment of cells is compatible with live-cell imaging studies; and finally, iii) treatment of cells with xenobiotics-spiked and normal milk derived fat provides a visual and quantifiable response of NR translocation in living cells. Utilizing a milk-fat extraction method and Green Fluorescent Protein (GFP) tagged NRs expressed in cultured mammalian cells, followed by an assessment of NR response proved to be an effective approach for screening xenobiotics present in milk samples.HighlightsDiverse endocrine and metabolism-disrupting chemicals are suspected to contaminate milk.Nuclear receptors serve as 'xenosensors' for assessing the presence of xenobiotics in milk.Nuclear import of steroid receptors with (ant)agonist can be examined in live cells.Lipophilic xenobiotics are extracted and observed enriched in milk-fat fraction.A comprehensive cell-based protocol aids in the detection of xenobiotics in milk.

Mitochondria-actin cytoskeleton crosstalk in cell migration.

Mitochondria perform diverse functions in the cell and their roles during processes such as cell survival, differentiation, and migration are increasingly being appreciated. Mitochondrial and actin cytoskeletal networks not only interact with each other, but this multifaceted interaction shapes their functional dynamics. The interrelation between mitochondria and the actin cytoskeleton extends far beyond the requirement of mitochondrial ATP generation to power actin dynamics, and impinges upon several major aspects of cellular physiology. Being situated at the hub of cell signaling pathways, mitochondrial function can alter the activity of actin regulatory proteins and therefore modulate the processes downstream of actin dynamics such as cellular migration. As we will discuss, this regulation is highly nuanced and operates at multiple levels allowing mitochondria to occupy a strategic position in the regulation of migration, as well as pathological events that rely on aberrant cell motility such as cancer metastasis. In this review, we summarize the crosstalk that exists between mitochondria and actin regulatory proteins, and further emphasize on how this interaction holds importance in cell migration in normal as well as dysregulated scenarios as in cancer.

Synthetic Control of Exciton Dynamics in Bioinspired Cofacial Porphyrin Dimers.

Understanding how the complex interplay among excitonic interactions, vibronic couplings, and reorganization energy determines coherence-enabled transport mechanisms is a grand challenge with both foundational implications and potential payoffs for energy science. We use a combined experimental and theoretical approach to show how a modest change in structure may be used to modify the exciton delocalization, tune electronic and vibrational coherences, and alter the mechanism of exciton transfer in covalently linked cofacial Zn-porphyrin dimers (meso-beta linked ABm-ß and meso-meso linked AAm-m). While both ABm-ß and AAm-m feature zinc porphyrins linked by a 1,2-phenylene bridge, differences in the interporphyrin connectivity set the lateral shift between macrocycles, reducing electronic coupling in ABm-ß and resulting in a localized exciton. Pump-probe experiments show that the exciton dynamics is faster by almost an order of magnitude in the strongly coupled AAm-m dimer, and two-dimensional electronic spectroscopy (2DES) identifies a vibronic coherence that is absent in ABm-ß. Theoretical studies indicate how the interchromophore interactions in these structures, and their system-bath couplings, influence excitonic delocalization and vibronic coherence-enabled rapid exciton transport dynamics. Real-time path integral calculations reproduce the exciton transfer kinetics observed experimentally and find that the linking-modulated exciton delocalization strongly enhances the contribution of vibronic coherences to the exciton transfer mechanism, and that this coherence accelerates the exciton transfer dynamics. These benchmark molecular design, 2DES, and theoretical studies provide a foundation for directed explorations of nonclassical effects on exciton dynamics in multiporphyrin assemblies.

Fluorescent xylitol carbon dots: A potent antimicrobial agent and drug carrier.

Biomolecular carbon dots (CDs) have immense potential for various industries due to exceptional bioactivity, biocompatibility, low toxicity, and biodegradability. In the present work xylitol (Xlt), a natural sweetener produced by microbial fermentation of sugarcane bagasse (71.98% conversion) has been used for CDs preparation by microwave-assisted carbonization in the presence of ethylene diamine (EDA). The resultant xylitol carbon dots (XCDs) were irregular shaped, rough with an average size of 8.88 nm and exhibiting fluorescence between 400 and 450 nm. The presence of EDA preserves the native chemical structure of Xlt even after exposure to microwaves. Purified XCDs were conjugated (AM-XCD) with ketoconazole and tetracycline for fungi and bacteria, respectively. In comparison to Xlt, XCDs have higher inhibitory potential and reduced dosage size of antimicrobials against Cryptococcus neoformans, Candida albicans, Streptococcus pyogenes, and Escherichia coli by 75%, 75%, 87.50%, and 50%, respectively. For Listeria monocytogenes and Salmonella typhi also inhibitory potential was increased by 14.68% and 21.38%. Increased efficacy advocated the improved drug delivery in the presence of XCDs. However, no inhibitory effect was recorded against DU145 (human prostate cancer) and HCT-15 (human colon adenocarcinoma) cell lines. The findings of the current work suggested the possible use of Xlt as an important antimicrobial agent besides an efficient drug carrier in healthcare.

Rapid assessment of plant diversity using MODIS biophysical proxies.

The spectral information derived from satellite data provides important inputs for assessing plant diversity. If a suitable satellite-derived biophysical proxy is applicable to assess and monitor plant diversity of different biogeographic regions will be of interest to policy makers and conservationists. We selected four biogeographic regions of India, i.e., semi-arid, Eastern Ghats, Western Ghats, and Northeast as the test sites on the basis of variations in moisture availability. The flora data collected for the study sites are the extract of the national biodiversity project 'Biodiversity Characterization at Landscape Level'. The available Moderate Resolution Imaging Spectroradiometer (MODIS)-derived biophysical proxies at high temporal frequencies was considered to compare the biophysical proxies: surface reflectance-red and near-infrared, normalized difference vegetation index-NDVI, enhanced vegetation index-EVI, leaf area index-LAI, and fraction of absorbed photosynthetically active radiation-FAPAR at different temporal scales (monthly, post-monsoon, seasonal, annual) in each selected biogeographic regions of India. Generalized linear model (GLM) and multivariate adaptive regression spline (MARS) were utilized to evaluate the relationship between plant diversity and MODIS-derived biophysical proxies. MARS summarized the suitable biophysical proxies at monthly scale in descending order for the total forest area in semi-arid was red, NDVI, and FAPAR; for Eastern Ghats was EVI, FAPAR, and LAI; for Western Ghats was EVI, LAI, and FAPAR; and for Northeast was NDVI, near-infrared, and red. Furthermore, monthly FAPAR commonly found to be the suitable proxy to large scale monitoring of plant diversity in the moisture-varied biogeographic regions of India, except Northeast. Using artificial neural network, the relationship of plant diversity and monthly FAPAR/NDVI were modeled. The correlation between the predicted and reference plant diversity was found to be r = 0.56 for semi-arid, r = 0.52 for Eastern Ghats, r = 0.52 for Western Ghats and r = 0.61 for Northeast at p-value < 0.001. The study affirms that FAPAR is potentially an essential biodiversity variable (EBV) for carrying out rapid/indicative assessment of plant diversity in different biogeographic regions, and thereby, meeting various international commitments dealing with conservation and management measures for biodiversity.

Global footprints of organochlorine pesticides: a pan-global survey.

Organochlorine pesticides (OCPs) are ubiquitous environmental contaminants widely used all over the world. These chlorinated hydrocarbons are toxic and often cause detrimental health effects because of their long shelf life and bioaccumulation in the adipose tissues of primates. OCP exposure to humans occurs through skin, inhalation and contaminated foods including milk and dairy products, whereas developing fetus and neonates are exposed through placental transfer and lactation, respectively. In 1960s, OCPs were banned in most developed countries, but because they are cheap and easily available, they are still widely used in most third world countries. The overuse or misuse of OCPs has been rising continuously which pose threats to environmental and human health. This review reports the comparative occurrence of OCPs in human and bovine milk samples around the globe and portrays the negative impacts encountered through the long history of OCP use.

Moderate resolution LAI prediction using Sentinel-2 satellite data and indirect field measurements in Sikkim Himalaya.

The leaf area index (LAI) has been traditionally used as a photosynthetic variable. LAI plays an essential role in forest cover monitoring and has been identified as one of the important climate variables. However, due to challenges in field sampling, complex topography, and availability of cloud-free optical satellite data, LAI assessment on larger scale is still unexplored in the Sikkim Himalayan area. We used two optical instruments, digital hemispherical photography (DHP) and LAI-2200C, to assess the LAI across four different forests following 20 × 20 m2 elementary sampling units (ESUs) in the Himalayan state of Sikkim, India. The use of Sentinel-2 derived vegetation indices (VIs) demonstrated a better correlation with the DHP based LAI estimates than using LAI-2200C. Further, the combination of both reflectance bands and VIs were integrated to predict the LAI maps using random forest model. The temperate evergreen forests demonstrated the highest LAI value, while the predicted maps exhibited LAI maxima of 3.4. The estimated vs predicted LAI for DHP and LAI-2200C based estimation demonstrated reasonably good (R2 = 0.63 and R2 = 0.68, respectively) agreement. Further, improvements on the LAI prediction can be attempted by minimizing errors from the inherent field protocols, optimizing the density of field measurements, and representing heterogeneity. The recent rise of frequent forest fires in Sikkim Himalaya prompts for better understanding of fuel load in terms of surface fuel or canopy fuel that can be linked to LAI. The high-resolution LAI map could serve as input to forest fuel bed characterization, especially in seasonal forests with significant variations in green leaves and litter, thereby offering inputs for forest management in changing climate.

Disruption of profilin1 function suppresses developmental and pathological retinal neovascularization.

Angiogenesis-mediated neovascularization in the eye is usually associated with visual complications. Pathological angiogenesis is particularly prominent in the retina in the settings of proliferative diabetic retinopathy, in which it can lead to permanent loss of vision. In this study, by bioinformatics analyses, we provide evidence for elevated expression of actin-binding protein PFN1 (profilin1) in the retinal vascular endothelial cells (VECs) of individuals with proliferative diabetic retinopathy, findings further supported by gene expression analyses for PFN1 in experimentally induced abnormal retinal neovascularization in an oxygen-induced retinopathy murine model. We observed that in a conditional knockout mouse model, postnatal deletion of the Pfn1 gene in VECs leads to defects in tip cell activity (marked by impaired filopodial protrusions) and reduced vascular sprouting, resulting in hypovascularization during developmental angiogenesis in the retina. Consistent with these findings, an investigative small molecule compound targeting the PFN1-actin interaction reduced random motility, proliferation, and cord morphogenesis of retinal VECs in vitro and experimentally induced abnormal retinal neovascularization in vivo In summary, these findings provide the first direct in vivo evidence that PFN1 is required for formation of actin-based protrusive structures and developmental angiogenesis in the retina. The proof of concept of susceptibility of abnormal angiogenesis to small molecule intervention of PFN1-actin interaction reported here lays a conceptual foundation for targeting PFN1 as a possible strategy in angiogenesis-dependent retinal diseases.